Tenofovir disoproxil fumarate treatment was not linked to adverse perinatal outcomes in pregnant women with HIV in Kenya and Uganda, a prospective analysis found.

“As global elimination of mother-to-child transmission efforts intensify by expanding [prevention of mother-to-child transmission] Option B+ and as PrEP use expands among pregnant women worldwide, the likelihood of women using [tenofovir disoproxil fumarate] during pregnancy will substantially increase in settings where HIV prevalence is high,” Renee Heffron, PhD, of the University of Washington, Seattle, and colleagues wrote.

The researchers noted that the Promoting Maternal-Infant Survival Everywhere (PROMISE) study reported that African mothers with HIV who used tenofovir disoproxil fumarate (TDF) experienced higher rates of adverse perinatal outcomes such as very preterm birth, low birth weight and early infant death. Further, in a large systematic review that found no significant differences between mothers who did and did not use TDF, several prospective studies showed mixed results.

The researchers performed a longitudinal analysis of women who were pregnant during the Partners PrEP Study, a randomized clinical trial of PrEP, and the Partners Demonstration Project, an open-label study on PrEP and ART for preventing HIV infection (n = 422 pregnancies). Heffron and colleagues used multivariate models to identify associations between prenatal tenofovir disoproxil fumarate treatment and perinatal outcomes.

The women had a median age of 25.4 years. Slightly more than one-fifth (21%) of a total of 422 pregnancies were first-time pregnancies, the researchers reported.

The two most common ART regimens were tenofovir disoproxil fumarate (39%) and zidovudine (34%), Heffron and colleagues wrote. Tenofovir disoproxil fumarate exposure occurred in nearly half (49%) of pregnancies, and a protease inhibitor was used in 6% of pregnancies.

Neonatal death occurred in 2% of cases, the researchers reported, whereas preterm birth occurred in 8% of cases and pregnancy loss occurred in 12%. However, Heffron and colleagues wrote that there was no difference in pregnancy loss between those that included tenofovir disoproxil fumarate exposure and those that did not (adjusted prevalence rate ratio, 1.19; P = 0.8); the same held true for neonatal death (P = 0.6). Pregnancies that were exposed to tenofovir disoproxil fumarate demonstrated a lower prevalence of preterm birth (adjusted prevalence rate ratio, 0.34; P = .02), the researchers reported.

In a blog post published in the New England Journal of Medicine, Paul E. Sax, MD, professor of medicine at Brigham and Women’s Hospital, called the findings “reassuring.” Sax also pointed out that the study contradicted guidelines recently published in the British Medical Journal, which recommended ART with zidovudine during pregnancy.

“We know from thirty years of experience that zidovudine has considerable toxicity — subjective side effects such as nausea and headache, and additional problems related to mitochondrial toxicity, including bone marrow suppression, lipoatrophy, and lactic acidosis,” Sax wrote.

“As a result, it’s very hard to imagine prescribing zidovudine again under any circumstances, including during pregnancy. Today, the most commonly used initial regimen at our hospital during pregnancy is TDF/FTC and raltegravir; if patients are on a successful treatment and become pregnant, we generally continue that, almost regardless of what it is.” – by Andy Polhamus